Serum response factor (SRF) is a transcription factor which regulates a number of immediate early genes, thereby mediating the rapid transcriptional response to extracellular stimuli (eg, growth, stress, or differentiation signals; Norman et al., 1988). DNA-protein complexes containing SRF function as nuclear targets of the Ras/MAPK signalling network (Gille et al., 1992). A number of studies imply important roles for SRF in the development and functioning of important organs such as heart, muscle, and brain (Croissant et al., 1996; Arsenian et al., 1998). Mouse Srf is encoded on chromosome 17. We showed previously that a constitutive, homozygous null mutation of the murine Srf gene leads to early embryonic lethality (Arsenian et al., 1998). Normal development of SRF deficient embryos ceases before E6. 5, the point of mesoderm formation, and the embryos fail to express the mesodermal marker genes T/Brachyury and Bmp2. To investigate later roles of SRF in mouse development and in adulthood, we have created a genomic floxed Srf allele (named Srf-flex1 for floxed exon1) permitting conditional generation of null alleles using the Cre/loxP system.

Conditional Cre-mediated recombination at the Srfflex1 locus (Fig. 1A) generates a deletion identical to that in the previously reported constitutive null allele (Arsenian et al., 1998). The deletion spans the complete coding region of Srf exon 1. In the targeting vector, the first loxP-site is positioned in the 5!-untranslated region of the Srf gene, the second and third surrounding the MC1-neo positive selection marker within intron 1 (Fig. 1A).